High throughput is one of many advantages and goals of Micro-Total-Analysis-Systems or Lab-on-a-Chip systems. High throughput often means either assaying multiple samples at one time or conducting multiple assays for one sample, or both. For the case of assaying multiple samples at one time, processing simultaneously or in parallel is a basic requirement for valid data analysis and result comparisons. For a typical biological assay, each sample is further subject to multiple steps of processing before its characteristics or compositions being determined. These steps include, but not limited to, reaction, separation, dilution, purification, extraction, washing, mixing, etc. Each of the steps may involve a different reagent or buffer fluid that is common to all samples.
Clearly, it is more efficient to distribute common fluids to different multiple processing units in parallel than to fill them one by one. For a multiplexed assay, different samples or reagent fluids may be loaded at first to each of the multiple processing units, or, different reagents may be deposited in advance to the multiple processing units in dry form. Reactions in the processing channels may be either homogeneous (e.g., RT-PCR) or heterogeneous (e.g., a microarray assay). For multi-step protocols (e.g., most immunoassay protocols), more than one common reagent fluids may be applied in sequence, and a common fluid is desirable to be ‘flushed’ (i.e., fluid being emptied and air being introduced) before next fluid is introduced. Air may be applied between any two common liquid fluids. It is desirable that the flushing process be in parallel through the multiple processing units to avoid potential shortcut.
When multiple processing units are delivered and emptied with fluid for many times, air bubbles may be formed and trapped because it is practically impossible for fluids to be flowed in an exactly synchronous fashion within the multiple processing units. Any slight flow imbalance could easily add up each time and quickly disrupt the concurrence in the multiple processing units. The flow imbalance may be resulted from inexactness of geometry among multiple processing units, and  is further complicated by random surface effect, particularly in the presence of air bubbles once formed.
Various microfluidic systems have been developed for improving fluid control in multi-channeled high throughput processes. In some systems, a cascading channel-splitting structure is provided to make the paths from each of the multiple processing units to a common fluid source equidistantly. It has been further known that a fluidic flow may randomly choose one branch over the other at a channel split owing to surface effect. Therefore, ever-decreasing channel dimensions towards the last level of cascading is often practiced so that corresponding ever-increasing flow resistance would help overcome the surface effect experienced at upper levels of channel-splitting. However, such a structure works poorly as it is flushed by air, because it is very difficult to expel any liquid fluid out of the smallest capillaries in a channeled fluidic network. As number of common fluids increases, each with its own cascading channel-splitting structure so as to avoid flushing by air, undesirable cross intersection of channels occurs if they are put on the same 2-D plane. In order to solve this problem, a rather complex multi-layered fluid distributing structure has been developed. See, e.g., U.S. Pat. Nos. 6,880,576 and 6,981,522. These two patents disclose microfluidic devices with multiple fluid process regions for subjecting similar samples to different process conditions in parallel. In these devices, one or more common fluid inputs may be provided to minimize the number of external fluid supply components. U.S. Pat. No. 6,499,499 discloses an elevated flow resistance microfluidic structure and method thereof to distribute a fluid into multiple channels in parallel, which, however, is insufficient to accomplish further repetitive flushing and distributing steps in parallel for multi-step assays. The U.S. Patent application 2006210439-A1 discloses a method in which a fluidic device is pre-vacuumed and a common sample fluid is then made possible to autonomously occupy multiple dead-end processing channels, however, the task of emptying channels in parallel is very difficult, if not totally impossible, with the dead-end microfluidic structure, hence a multi-step assays cannot be readily achieved. There remains a need to develop a microfluidic device to efficiently delivering and emptying multiple processing channels in parallel.
All patents, patent applications, and publications cited herein are hereby incorporated by reference in their entirety. 